Effect of selegiline on free radical oxidation in the brain of rats with alloxan diabetes

Introduction. Hyperglycemia in diabetes mellitus (DM), accompanied by the development of oxidative stress, is the cause of long-term complications in the peripheral and central nervous system. Several leading redox-dependent mechanisms of diabetic neuropathy have been described, among which monoamine oxidases (MAO) play an important role. The brain is characterized by high activity of monoamine oxidases, which are active producers of hydrogen peroxide. Meanwhile, the contribution of monoamine oxidases to the development of oxidative stress in the brain under conditions of long-term hyperglycemia remains unexplored.

Purpose of the study - to determine the contribution of monoamine oxidases to the development of oxidative stress in the brain under conditions of alloxan-induced hyperglycemia.

Material and methods. The study was conducted on 111 mature Wistar rats of both sexes, weighing 180-250 grams. Diabetes mellitus was modeled by intraperitoneal administration of alloxan monohydrate at a dose of 163 mg/kg. To assess the contribution of MAO to the development of oxidative stress, a selective MAO-B inhibitor selegiline was used at a daily dose of 5 mg/kg. Throughout the experiment, glycemia and body weight of the animals were monitored. The animals were withdrawn from the experiment on the fourteenth day after alloxan administration. The levels of oxidative modification of proteins, lipid peroxidation products, and the activity of monoamine oxidases A and B in brain homogenates were determined by spectrophotometric methods.

Results. On the fourteenth day after alloxan administration, signs of oxidative stress (increased oxidative modification of proteins) are detected in the brain. The results of the correlation analysis demonstrate direct relationships in the Alloxan group of animals between the blood glucose level on the 14th day of the experiment and the levels of protein oxidative modification products, as well as MAO-B activity and the levels of protein oxidative modification products. The absence of such relationships in the group of animals additionally receiving the MAO inhibitor (Alloxan + selegiline), as well as the control levels of MAO-B products in the brain of this group of animals, confirm the contribution of intensification of free radical oxidation to the development of diabetic neuropathy with prolonged hyperglycemia, on the one hand, and the prooxidant effect of MAO, on the other.

Conclusions. The results of the study confirm the contribution of alloxan-induced hyperglycemia to MAO-dependent oxidative modification of proteins in the brain.